The present invention relates to a process for preparing quinoline-5,8-diones which find an application as intermediate products, especially in the pharmaceutical industry.
Bracher (Heterocycles, 29, 2093, 1989) has already mentioned a process for preparing quinoline-5,8-dione from 5-amino-8-hydroxyquinoline by oxidation with dichromate. This process requires a double functionalization of the quinoline nucleus, and thus involves starting materials that are expensive and not readily available. S. Ghosh (J. Fluorine Chem., 1994; 67: 53-56) describes quinoline-5,8-dione derivatives obtained by cycloaddition between p-benzoquinone and a substituted diene. 4-Chloroquinoline-5,8-dione is described as a synthetic intermediate of more complex tricyclic or tetracyclic compounds (M. Croisy-Delsey et al., J. Heterocyclic Chem. 1993; 30: 55-60), whereas 2-methoxyquinoline-5,8-dione is presented as a by-product of the N-alkylation of 2,5,8(1H)-quinolinetrione (C. Avendano et al. Synthesis 1991; 727-730). 4-Hydroxy-5,8-quinolinequinone may be synthesized from 2,5-dimethoxyaniline and from the ester of methylacrylic acid (P. Withopf et al. Tetrahedron, 1987; 43(20):4549-4554). Quinoline-5,8-dione and 2-chloro-4-methylquinoline-5,8-dione are starting materials used in the synthesis of azaanthraquinone derivatives (K. T. Potts et al., J. Org. Chem., 1986:2011-2021). Antimalaria agents derived from 6-amino-5,8-dimethoxyquinolines are prepared from 2-trifluoro-4-methyl or from 2,4-dimethyl quinoline-5,8-dione (C. Temple et al., J. Med. Chem., 1974; 17(6):615-619). Finally, EP 0 433 679 describes quinoline-5,8-dione derivatives as inhibitors of the Maillard reaction in the body, this reaction being responsible (by denaturing proteins via sugars) for several consequences of diabetes (neuropathy, retinopathy, etc.).
Methods also exist for preparing quinones by photo-oxidation of phenols (for example Chem. Comm., 2173, 1996), but it has never been envisaged to apply such methods to heterocyclic compounds and in particular to quinoline derivatives.
The reason for this is that it was not obvious that such methods would not be hampered by the presence of the electron-withdrawing pyridine nucleus. Reactions between the quinones and the nitrogen of the pyridine nucleus, leading to colored polymers, could also have been feared. This is what was observed with 5-hydroxyisoquinoline.
It has now been found that a particular group of 8-hydroxyquinolines gives, by photo-oxidation, in the presence of a sensitizer and decomposition of the intermediate hydroxyperoxide, quinoline-5,8-diones in high yields.
One subject of the present invention is a process for preparing quinoline-5,8-diones of formula: 
in which:
R1, R2 and R3 are chosen from hydrogen, a halogen atom, a C1-C6 alkyl group, xe2x80x94CHO, xe2x80x94OH, xe2x80x94OR, xe2x80x94COOH, xe2x80x94CN, xe2x80x94CO2R, xe2x80x94CONHR, xe2x80x94CONRRxe2x80x2xe2x80x94, xe2x80x94NH2, xe2x80x94NHCOR, 
xe2x80x83morpholino and SO3H, R and Rxe2x80x2 being chosen from C1-C6 alkyl groups and Ar being a C6-C14 aryl group,
in which an 8-hydroxyquinoline of formula: 
in which R1, R2 and R3 have the meaning given above, is oxidized with oxygen under the action of actinic radiation in solution in an organic solvent and in the presence of a catalytic amount of a sensitizer, and the hydroperoxide formed, of formula: 
is then decomposed to a compound of formula I.
The oxidation reaction with oxygen is carried out in an organic solvent in which the starting 8-hydroxyquinoline of formula II is soluble. The solvent is advantageously chosen such that the sensitizer is also soluble therein.
The sensitizer may especially be tetraphenylporphine (or TPP), in which case the solvent may especially be dichloromethane.
Other suitable sensitizers and solvents may also be used, and in particular:
rose bengal in CH3CN, MeOH, EtOH, CHCl3 or water;
methylene blue in CH3CN, MeOH, EtOH, CHCl3 or water;
tetra(4-pyridyl)porphine in CH2Cl2 or CHCl3;
dicyanonaphthalene (DCN), dicyanoanthracene (DCA) or dicyanobenzene (DCB);
N,Nxe2x80x2-dimethyl-2,7-diazapyrenium (DAP2+) bis(tetrafluoroborate).
The reaction is advantageously carried out in the region of room temperature (15 to 25xc2x0 C.) under irradiation, with visible light while sparging with oxygen, for a period which may be from 2 to 8 hours.
The hydroperoxide formed, of formula III, spontaneously decomposes with stirring, especially in the presence of Na2SO4.
A subject of the present invention is also the quinoline-5,8-diones of formula: 
in which:
R1, R2 and R3 are chosen from hydrogen, a halogen atom, a C1-C6 alkyl group, xe2x80x94CHO, xe2x80x94OH, xe2x80x94OR, xe2x80x94COOH, xe2x80x94CN, xe2x80x94CO2R, xe2x80x94CONHR, xe2x80x94CONRRxe2x80x2xe2x80x94, xe2x80x94NH2, xe2x80x94NHCOR, 
xe2x80x83morpholino and SO3H, R and Rxe2x80x2 being chosen from C1-C6 alkyl groups and Ar being a C6-C14 aryl group,
with the exception of the compounds in which:
R1=H, R2=H and R3 is chosen from H, CH3, CN and CHO,
R1=H or CH3, R2=F and R3=H p1 R1=Cl, R2=H and R3=H
R1=OH, R2=H and R3=COOH, COOCH3 or CH3 
R1=OH, R2=COOH or COOC2H5 and R3=H
R1=H, R2=H and R3=OCH3 
R1=OH, R2=H and R3=H
R1=OCH3, R2=H and R3=H
R1=CH3, R2=H and R3=Cl
R1=CH3, R2=H and R3=CH3